Instituto de Investigaciones Bioquímicas de La Plata-Pathology B, Faculty of Veterinary Medicine, University of La Plata, 1900 La Plata, Argentina.
Endocrinology. 2012 Aug;153(8):3922-8. doi: 10.1210/en.2012-1183. Epub 2012 Jun 14.
Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis.
先天性无胸腺（裸体）雌性小鼠在青春期后表现出严重的卵巢发育不良，这似乎与这些突变体中描述的许多神经内分泌紊乱有关。因此，大量证据表明，胸腺素，一种胸腺肽，可能参与了胸腺-垂体的通讯。为了阐明胸腺素对雌性生殖系统成熟的相关性，我们评估了下丘脑、垂体、卵巢和子宫水平上，新生期胸腺素基因治疗（NTGT）对先天性无胸腺雌性小鼠青春期后典型变化的预防作用。我们在新生无胸腺裸鼠（胸腺素缺乏）中注射（肌内）携带编码生物活性胸腺素类似物（蛋氨酸-血清胸腺因子）的合成 DNA 序列的腺病毒载体，并在 70-71 日龄时处死动物。NTGT 在无胸腺小鼠中恢复了血清胸腺素水平。形态计量学分析显示，无胸腺裸鼠的脑 GnRH 神经元和垂体促性腺细胞数量减少，与杂合子对照相比。NTGT 预防了这些变化，并挽救了无胸腺裸鼠中典型的卵巢早衰表型（窦前卵泡和黄体数量减少，闭锁卵泡增加）。无胸腺裸鼠的血清雌激素水平（而非孕激素水平）较低，这一降低部分被 NTGT 预防。雌性裸鼠的子宫内膜几乎没有形态变化。无胸腺裸鼠阴道开口年龄的延迟被 NTGT 显著预防。我们的结果表明，胸腺素在胸腺-下丘脑-垂体-性腺轴中发挥着重要的生理作用。
